MutS homolog 5 (MSH5) is a member of a family of proteins that are known to be involved in DNA mismatch repair (Modrich, P. & Lahue (1996) Annu. Rev. Biochem. 65, 101–133; Kolodner, R. (1996) Genes Dev. 10, 1433–1442). Germ line mutations in MSH2, MLH1 and MSH6 cause hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome (Leach, F. S. et al. (1993) Cell 75, 1215–1225; Bronner, C. E. et al. (1994) Nature 368, 258–261; Papadopoulos, N. et al. (1994) Science 263, 1625–1629; Akiyama, Y. et al. (1997) Cancer Res. 57, 3920–3923; Miyaki, M. et al. (1997) Nature Genet. 17, 271–272). Inactivation of Msh2, Mlh1, Msh6 and Pms2 in mice leads to hereditary predisposition to intestinal and other cancers (de Wind, N. et al. (1995) Cell 82, 321–330; Reitmair, A. H. et al. (1995) Nature Genet. 11, 64–70). Early studies in yeast revealed a role for some of these proteins, including MSH5, in meiosis (Hollingsworth, N. M., et al. (1995) Genes & Development 9, 1728–1739; Ross-Macdonald, P. & Roeder, G. S. (1994) Cell 79, 1069–1080). Gene targeting studies in mice confirmed roles for MLH1 and PMS2 in mammalian meiosis (Baker, S. M. et al. (1995) Cell 82, 309–320; Edelmann, W. et al. (1996) Cell 85, 1125–1134; Baker, S. M. et al. Nature Genet. 13, 336–342).